A Study to Test How Well Different Doses of BI 754132 Are Tolerated in Patients With an Advanced Form of Age-related Macular Degeneration Called Geographic Atrophy

Safety, Tolerability and Pharmacokinetics of Single Rising Intravitreal Doses and Multiple Intravitreal Dosing of BI 754132 in Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration (Open Label, Non-randomized, Uncontrolled).

This is a study in adults with geographic atrophy, an advanced form of age-related macular degeneration. The purpose of this study is to find out how well different doses of BI 754132 are tolerated.

The participants are in the study for about 4 months. During this time, they visit the study site about 10 times. Participants receive 1 injection of BI 754132 directly into one of the eyes affected by geographic atrophy. In this study, BI 754132 is given to humans for the first time.

The doctors compare how well participants tolerate the different doses of BI 754132. The doctors also regularly check the general health of the participants.

Study Overview

• Status: Terminated
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: BI 754132

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom, BS1 2LX
    • Bristol Eye Hospital
  • Liverpool, United Kingdom, L69 3GA
    • Royal Liverpool University Hospital
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Retina-Vitreous Associates Medical Group
  • Florida
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Winter Haven, Florida, United States, 33880
      • Center for Retina and Macular Disease
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center, PC
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associate PA
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina
  • Texas
    • Bellaire, Texas, United States, 77401
      • Retina Consultants of Texas
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

- Men and women with Geographic Atrophy (GA) secondary to Age-related Macular Degeneration (AMD): For the SRD part, the GA lesion in the study eye must be ≥ 1.9 mm2 disc area in size (approximately ≥ 0.75 disc area in size); For the MD part the total GA lesion size in the study eye must be ≥ 7.5 mm2 (approximately ≥ 3 disc area in size)

• Fellow eye is not required to have GA

• Best Corrected Visual Acuity (BCVA):

  • SRD part: BCVA of 20/100 to 20/400 Snellen (corresponding to 19 to 53 letters in the ETDRS chart) in the study eye equivalent measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol
  • MD part: BCVA score of ≤53 letters (Snellen equivalent of 20/100) in the study eye
• Age ≥ than 50 years
• Best-corrected VA in the non-study eye must have a better best-corrected VA compared to the study-eye
• Women of childbearing potential (WOCBP) cannot be included. Men able to father a child must be ready and able to use highly effective methods of birth control per International Council on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
• Signed informed consent consistent with International Council on Harmonisation Good Clinical Practice (ICH GCP) guidelines and local legislation prior to participation in the trial, which includes medication washout and restrictions
• Not under any administrative or legal supervision or under institutionalization due to regulatory or juridical order

Exclusion criteria

• GA in either eye because of causes other than AMD
• History of choroidal neovascularization (CNV) in the study eye and in the fellow eye
• Previous treatment in the study eye for GA secondary to AMD within 6 months prior to screening visit (ongoing therapy with vitamin and mineral supplements is allowed)

• Additional eye disease in the study eye that could compromise

  • best corrected VA (BCVA) with visual field loss,
  • uncontrolled glaucoma intraocular pressure (IOP>24),
  • clinically significant diabetic maculopathy,
  • history of ischemic optic neuropathy or retinal vascular occlusion,
  • symptomatic vitreomacular traction,
  • genetic disorders such as retinitis pigmentosa);
  • history of high myopia > 8 diopters in the study eye and
  • anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation with Spectral Domain Optical Coherence Tomography (SD-OCT)
• Any prior intraocular surgery in the study eye other then uneventful lens replacement for cataract within 3 months prior to screening
• Aphakia or total absence of the posterior capsule. Yttrium aluminum garnet (YAG) laser capsulotomy permitted, more than 3 month prior to enrollment in the study eye
• Current or planned use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol)

• Significant disease or other medical conditions (as determined by medical history, examination and clinical investigations at screening) that may, in the opinion of the investigator result in the any of the following:

  • Put the patient at risk because of participation in the study
  • Influence the results of the study,
  • Cause concern regarding the patient's ability to participate in the study, e.g. cardiac (including tachycardia), gastro-intestinal, hepatic, renal, metabolic, dermatologic, neurological, haematological, oncological and psychiatric.
• Patients with malignancy for which the patient has undergone resection, radiation or chemotherapy within past 5 years. Patients with treated basal cell carcinoma or fully cured squamous cell carcinoma are allowed.
• Known hypersensitivity to any of the ingredients used in the Investigational Medical Product (IMP) formulation, or any of the medications used
• Active intraocular inflammation in the study eye
• Active infectious conjunctivitis in either eye
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.3 mg BI 754132 - SRD part; 0.3 milligram (mg) BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as one single injection on Day 1. One patient was dosed first, and when the safety assessments through Day 4 showed no ophthalmological dose limiting events (DLEs) or systemic DLEs, the remaining patients were dosed. Single rising dose (SRD) part.	Drug: BI 754132; One single injection
Experimental: 1 mg BI 754132 - SRD part; 1 mg BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as one single injection on Day 1. One patient was dosed first, and when the safety assessments through Day 4 showed no ophthalmological dose limiting events (DLEs) or systemic DLEs, the remaining patients were dosed. SRD part.	Drug: BI 754132; One single injection
Experimental: 3 mg BI 754132 - SRD part; 3 mg BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as one single injection on Day 1. One patient was dosed first, and when the safety assessments through Day 4 showed no ophthalmological dose limiting events (DLEs) or systemic DLEs, the remaining patients were dosed. SRD part.	Drug: BI 754132; One single injection
Experimental: 6 mg BI 754132 - SRD part; 6 mg BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as one single injection on Day 1. One patient was dosed first, and when the safety assessments through Day 4 showed no ophthalmological dose limiting events (DLEs) or systemic DLEs, the remaining patients were dosed. SRD part.	Drug: BI 754132; One single injection
Experimental: 6 mg BI 754132 - MD part; 6 mg BI 754132 powder for solution for injection 60mg/vial with solution of diluent was administered intravitreally as 3 injections, each separated by 4 weeks (that is, Day 1, Day 29 and Day 57). Multiple dose.	Drug: BI 754132; One single injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SRD Part: Number of Patients With Ocular (in the Study Eye) or Systemic Dose Limiting Events (DLEs)	SRD part: Number of patients with ocular or systemic DLEs from drug administration. Systemic DLEs were defined as drug-related adverse events (AEs), as defined by the investigator, of moderate or severe intensity on the Common terminology criteria for adverse events (CTCAE) scale, and included diarrhea, cough, or patient-reported paraesthesia, dysgeusia, taste abnormality, taste disorder, or hyposmia. Single rising dose (SRD) part.	From drug administration until end of trial, up to 100 days.
MD Part: Number of Patients With Drug Related Adverse Events (AEs)	Number of patients with drug-related adverse events (AEs). Multiple dose (MD) part.	From drug administration until end of trial, up to 155 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SRD Part: Number of Patients With Drug-related Adverse Events (AEs)	Number of patients with drug-related AEs. Single rising dose (SRD) part.	From drug administration until end of trial, up to 100 days.
SRD Part: Number of Patients With Any Ocular Adverse Events (AEs) in the Study Eye	Number of patients with any ocular adverse events in the study eye. Single rising dose (SRD) part.	From drug administration until end of trial, up to 100 days.
SRD Part: Maximum Serum Concentration of BI 754132 After a Single Intravitreal Dose (Cmax)	Maximum serum concentration of BI 754132 after a single intravitreal dose (Cmax). Single rising dose (SRD) part.	At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
SRD Part: Area Under the Concentration-time Curve of BI 754132 in Serum Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	Area under the concentration-time curve of BI 754132 in serum over the time interval from 0 extrapolated to infinity (AUC0-∞). Singe rising dose (SRD) part.	At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
SRD Part: Time From Dosing to Maximum Serum Concentration of BI 754132 (Tmax)	Time from dosing to maximum serum concentration of BI 754132 (tmax). Single rising dose (SRD part).	At Day 1, 4, 8, 15, 29, 56, 84 and Day 100.
MD Part: Trough Levels of BI 754132 Before Second Administration (Cmin,1)	Systematic exposure of BI 754132 after multiple intravitreal doses as assessed by Cmin,1 (trough levels of BI 754132 before second administration). Multiple dose (MD) part.	Up to 29 days.
MD Part: Trough Levels of BI 754132 Before Third Administration (Cmin,2)	Systematic exposure of BI 754132 after multiple intravitreal doses as assessed by Cmin,2 (trough levels of BI 754132 before third administration). Multiple dose (MD) part.	Up to 57 days.
MD Part: Plasma Concentration of BI 754132 4, 8 and 14 Weeks After the Third Administration	Plasma concentration of BI 754132 4, 8 and 14 weeks after the third administration. Multiple dose (MD) part.	At Day 85, 113 and Day 155.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2019
• Primary Completion (Actual): August 9, 2022
• Study Completion (Actual): August 9, 2022

Study Registration Dates

• First Submitted: June 27, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): June 28, 2019

Study Record Updates

• Last Update Posted (Actual): September 15, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Pathological Conditions, Anatomical; Macular Degeneration; Geographic Atrophy; Atrophy
• Other Study ID Numbers: 1418-0001; 2018-004125-92 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No